1. Field of the Invention
The subject matter of the invention is a method and apparatus for rapid non-invasive determination of blood composition parameters.
2. Discussion of the Background
In medical diagnostics it is often necessary to determine various blood composition parameters, e.g. blood components like glucose, protein, albumin, creatinine, carbamide, cholesterol, triglyceride, cholinesterase, haemoglobin, etc. Measuring the glucose component is especially important, because diabetes mellitus seems to be considered as a widespread disease. For treatment of diabetes mellitus, glucose content of the blood must be regularly monitored. In line with up-to-date treatment principles, efforts must be made to close the gap as much as possible between the actual glucose component and the physiological one. Therefore, frequent blood sugar measurement is indispensable. Even under hospital conditions it is a frequent occurrence that only the determination of the glucose component is necessary. Today some diabetics determine their blood sugar themselves at home. This is primarily becoming a habit in areas having a developed health culture, but an objective should be to allow this opportunity for all patients.
There are widely used instruments which determine the glucose in blood by photometry using a blood drop on paper strips saturated with reagents. However, this approach is far from being perfect, because numerous circumstances, like the age of the paper strips, the temperature, the period elapsing between taking the blood sample and dripping it on the paper, make an unfavourable influence on the accuracy of measurement. But, the greatest concern is that the patient must be pricked in each case, because blood is required for the determination. Either the patient pricks himself or this is done by somebody else, sterility must be ensured. Even in the case of a patient really intending to cooperate, a very serious worry is the fact of being pricked. For a young diabetes patient, the glucose in blood must be controlled several times a day and this represents a lot of pricks throughout his lifetime as diabetes cannot be cured at the moment.
Therefore, it would be a major benefit to be able to determine blood components and especially glucose content by a non-invasive technology and, thereby, to eliminate the need of pricking the patient. The glucose component could be determined more frequently than now, which would enable more accurate adjustment, and so complications of diabetes could be better avoided. Even patients difficult to cope with would be more liable to measure the glucose in their blood themselves, because the measurement would be absolutely painless. Furthermore, infection could be avoided with total security. Materials necessary for disinfecting would not. be required neither reagents used so far for determining blood sugar, and this would have high significance also from an environment protection aspect as people in many hundreds of millions are involved all over the world.
It is well known that the spectrum of electromagnetic radiation reflected by or transmitted through a material contains valuable information about the composition of the examined material. For obtaining this information, numerous mathematical methods are available. Of these, worth mentioning are the "multiple linear regression" (MLR) method, which describes the correlation between spectrum values measured at some characteristic wavelengths and a component to be determined, as well as the "principal component regression" (PCR) and "partial least squares regression" (PLSR) methods which two latter methods describe the correlation between a component to be determined and so-called latent variables, where each of the latent variables can be generated as a function of all measured spectrum values in the form of a linear equation.
Organic materials, including body tissues, are most transparent in the near-infrared (NIR) wavelength range. It has already been suggested to use NIR technology for non-invasive determination of glucose in blood. Such apparatus have been described, for example, in U.S. Pat. Nos. 5,028,787, 5,777,476, 5,086,229, 5,237,178 and 5,362,966. These apparatus use NIR technology to measure glucose in blood in a part of the human body in transmission or interactance mode of operation, in a wavelength range from 600 to 1100 nm, where the penetration ability of electromagnetic radiation is the highest. In this wavelength range, the sensitivity of silicon detectors is also satisfactory. The apparatus described comprise infrared radiation sources, means for guiding the radiation to the examined part of the body, narrow-band filters, elements to position the body part in a measuring instrument, elements to measure the thickness of the body part, elements to measure and provide signal about the temperature of the body part and the environment, as well as detectors, amplifiers, signal processors and display units serving for measuring the radiation exiting from the body part. In signal processing, it has been recommended to use first and second derivatives of the measured spectrum and also a normalisation. As the point of measurement, the distal phalanx directly behind the nail, the nose, the earlobe and the vein visible at the wrist and the elbow-joint have been proposed.
A transmission detection technique in the long wavelength infrared range has been suggested in U.S. Pat. No. 5,313,941 to monitor glucose and other blood constituents in a non-invasive manner. Short pulses of relatively high energy and narrow optical bandwidth are sent through a finger which pulses are synchronised with the heartbeat period. The apparatus comprises a separate cardiac monitor which can be an optical plethysmograph or an electrocardiogram.
A spectrophotometric method for non-invasive measurement of component concentrations in body parts has been described in EP-A1-0 636 876. Pulsed laser light of different wavelength are projected toward a body part and the light exiting from the body part is detected. Then, by calculating an optimum lapse of time corresponding to an optimum path length, a quantity of the exiting light at the optimum lapse of time is determined. It has been suggested to utilize either transmitted light or reflected light or both, however, the description does not tell how to evaluate measurements if both transmitted and reflected lights are detected and what wavelengths of light are to be used.
So far, however, there is no available apparatus using NIR technology for non-invasive determination of glucose in blood that could be applied in a wide range of application with a sufficient accuracy.